LEAP FOR­WARD IN EYE TREAT­MENT TECHNOLOGY

EQUUS - - EQ MEDICALFRONT -

Treat­ing horses with fun­gal eye in­fec­tions may be sig­nif­i­cantly eas­ier in the fu­ture thanks to in­jectable ther­mo­gels that slowly re­lease med­i­ca­tion to a tar­geted lo­ca­tion for days, weeks or months.

Cur­rently, manag­ing a horse with ker­ato­my­co­sis, a fun­gal in­fec­tion of the cornea, can be ex­tremely dif­fi­cult. “The stan­dard use of an­ti­fun­gal med­i­ca­tions in ker­ato­my­co­sis con­sists of top­i­cal ap­pli­ca­tion from four to 12 times a day, de­pend­ing on the clin­i­cal signs and stage of the dis­ease,” says Eva M. Abarca, DVM, MS, DACVO, of the Univer­sity of Bern in Switzer­land. “This in­ten­sive treat­ment pro­to­col is chal­leng­ing in horses due to their lack of tol­er­ance for re­peated ap­pli­ca­tions of top­i­cal med­i­ca­tions, there­fore these in­ten­sive treat­ment pro­to­cols typ­i­cally re­quire the place­ment of an in­dwelling tub­ing sys­tem through which to ad­min­is­ter med­i­ca­tions.” Of­ten, horses must be ad­mit­ted to a clinic for the du­ra­tion of treat­ment, greatly in­creas­ing the cost.

Seek­ing to de­velop a more eco­nom­i­cal and prac­ti­cal treat­ment al­ter­na­tive, Abarca is work­ing with her for­mer col­leagues from the equine and in­ter­nal medicine and phar­macy de­part­ments at Auburn Univer­sity to in­ves­ti­gate the po­ten­tial of de­liv­er­ing an­ti­fun­gal med­i­ca­tions via ther­mo­gels in­jected un­der the eye’s con­junc­tiva.

“Ther­mo­gels are poly­mer so­lu­tions that are trans­formed into gels by changes in tem­per­a­ture,” she ex­plains. “This means that they can be in­jected as a liq­uid but form a gel de­posit upon reach­ing body tem­per­a­ture.”

When a med­i­ca­tion is mixed with the ther­mo­gel, it is slowly re­leased as the poly­mer breaks down over time. “De­pend­ing on the com­po­si­tion of the poly­mers this drug re­lease may be main­tained at the site of ad­min­is­tra­tion over days to months,” says Abarca.

In a re­cent study con­ducted at Auburn Univer­sity, the re­search group an­a­lyzed the re­lease rate of a ther­mo­gel con­tain­ing the an­ti­fun­gal drug voricona­zole and the de­gree to which the med­i­ca­tion per­me­ated corneal tis­sue. The data showed that voricona­zole was re­leased from the gel over the course of 21 days and dif­fused through the sclera and cornea of the equine eye. In ad­di­tion, the re­searchers de­ter­mined that upon re­lease from the ther­mo­gel, the drug re­tained its an­ti­fun­gal prop­er­ties.

These re­sults sug­gest that a voricona­zole-con­tain­ing ther­mo­gel could be used to

sim­plify the treat­ment of fun­gal eye in­fec­tions in horses: In­stead of mul­ti­ple daily treat­ments, a sin­gle in­jec­tion could po­ten­tially de­liver med­i­ca­tion for a sus­tained pe­riod. Al­though more re­search is needed to test this treat­ment pro­to­col in liv­ing horses with ac­tive dis­ease, in the opin­ion of the au­thors: “If the pro­posed ther­mo­gel proves ef­fec­tive, the con­tin­u­ous and sus­tained re­lease of voricona­zole within the eye may re­duce the fre­quency, length and cost of treat­ment re­quired in horses with ker­ato­my­co­sis and thus im­prove pa­tient com­fort, client com­pli­ance and clin­i­cal out­comes.”

Ac­cord­ing to a re­cently pub­lished study, a vac­cine to pro­tect horses from equine pro­to­zoal myeloen­cephali­tis (EPM) failed two sep­a­rate clin­i­cal tri­als.

Re­searchers at Ohio State Univer­sity worked with clin­i­cians at what was then Fort Dodge An­i­mal Health to test a killed-or­gan­ism vac­cine against Sar­co­cys­tis neu­rona, the pro­to­zoan that causes EPM. Fort Dodge An­i­mal Health was sub­se­quently ac­quired by Pfizer.

S. neu­rona is passed to horses by wildlife through con­tam­i­nated feed and wa­ter. The or­gan­ism is ubiq­ui­tous in many parts of the United States, and many horses are ex­posed to it with­out ill ef­fects. When S. neu­rona crosses the blood-brain bar­rier, how­ever, it at­tacks the brain and spinal cord lead­ing to neu­ro­log­i­cal im­pair­ment. Why that hap­pens isn’t com­pletely un­der­stood, but stress is be­lieved to make some horses more sus­cep­ti­ble.

For their vac­cine stud­ies, the re­searchers se­lected neu­ro­log­i­cally nor­mal horses that tested neg­a­tive for S. neu­rona. In the first ex­per­i­ment, re­searchers gave the horses ei­ther a vac­ci­na­tion fol­lowed by a booster in­jec­tion, or two placebo in­jec­tions on the same sched­ule. Thirty-four days af­ter the sec­ond in­jec­tion, the horses were then given feed con­tam­i­nated with S. neu­rona sporo­cysts.

For the sec­ond ex­per­i­ment, half the horses re­ceived an ini­tial vac­ci­na­tion fol­lowed by two booster in­jec­tions, while the other half re­ceived placebo shots at the same in­ter­vals. All of the horses were fed sporo­cyst­tainted feed 139 days af­ter the third in­jec­tion. Also, all of the horses were sub­jected to long trailer rides to in­crease their stress lev­els.

The re­searchers de­ter­mined that there was no sta­tis­ti­cal dif­fer­ence in the in­ci­dence of neu­ro­log­i­cal signs in­dica­tive of EPM be­tween the horses in the vac­ci­nated and placebo groups. Based on the two ex­per­i­ments, re­searchers con­clude that the vac­cine against S. neu­rona did not pre­vent the de­vel­op­ment of neu­ro­logic signs as­so­ci­ated with EPM.

Ref­er­ence: “Test­ing the Sar­co­cys­tis neu­rona vac­cine us­ing an equine pro­to­zoal myeloen­cephali­tis chal­lenge model,” Vet­eri­nary Par­a­sitol­ogy, Novem­ber 2017

NO SUC­CESS FOR EPM VAC­CINE The re­searchers de­ter­mined that there was no sta­tis­ti­cal dif­fer­ence in the in­ci­dence of neu­ro­log­i­cal signs in­dica­tive of EPM be­tween the horses in the vac­ci­nated and placebo groups.

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